Choline-O-sulfate (2-(trimethylammonio)ethyl sulfate, COS) is a naturally occurring osmolyte that is synthesized by plants, lichens, algae, fungi, and several bacterial species. We examined the inhibitory effects of COS on amyloid formation of the human islet amyloid polypeptide (hIAPP or amylin) using a thioflavin T (ThT) fluorescence assay, circular dichroism spectroscopy and transmission electron microscopy. The results showed that COS suppresses a conformational change of hIAPP from a random coil to a β-sheet structure, resulting in the inhibition of amyloid formation. Comparisons with various structural analogs including carnitine, acetylcholine and non-detergent sulfobetaines (NDSBs) using the ThT fluorescence assay showed that COS is the most effective inhibitor of hIAPP amyloid formation, suggesting that the sulfate group, which is unique to COS, significantly contributes to the inhibition.
Keywords: Aggregation inhibitor; Amyloid formation; CD, circular dichroism; COS, choline-O-sulfate; Choline-O-sulfate; HFIP, 1,1,1,3,3,3-hexafluoro-2-propanol; Islet amyloid polypeptide; NDSB, non-detergent sulfobetaine; Osmolyte; TEM, transmission electron microscopy; ThT, thioflavin T; hIAPP, human islet amyloid polypeptide.